Studies are aimed at the development of in vitro and in vivo models for investigating the role of arsenic (As) and other metals in carcinogenesis, particularly in epithelial tissues. Defined cell culture models were selected to study metal compounds for their metabolism, toxicity, carcinogenic activity and possible interaction with other xenobiotics. Initial studies were conducted using the mouse embryo cell line, BALB/3T3 clones A31-1-1, and primary cultures of epidermal cells also obtained from BALB/c mice. Induction of neoplastic transformation by As was obtained in BALB/3T3 clones A31-1-1 cultures; trivalent As was found to have higher toxicity than pentavalent As; trivalent As induced transformation foci at concentrations of 10E-5 and 10E-5.5 M, while pentavalent As was negative. The effects on mouse epidermal cells were studied after serum-free culture conditions were successfully optimized. In this system inorganic and direct-acting organic carcinogens were tested in a clonal assay to determine toxic dose-responses. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) showed a much lower effective toxic dose in this serum-free system than in equivalent serum-containing systems. The relative colony-forming efficiency was reduced to 25% by 10E-5 M trivalent As whereas pentavalent As did not inhibit colony-forming efficiency even at a ten-fold higher molarity. In the same epidermal cell system, hexavalent chromium (Cr) induced a high toxic response at doses from 3 x 10E-6 M to 3 x 10E-7 M whereas trivalent Cr was not toxic at doses as high as 10E-4 M. Transformation studies are under way and conditions will be defined for a qualitative and quantitative transformation assay for As and other metals in serum-free cultures of primary epidermal cells. The effects of As compounds on the respiratory tract epithelia will be investigated in the hamster model both in vivo and in vitro.